Ji Zhongqing, Zhu Jiangfeng, Liu Jinming, Wei Bin, Shen Yixin, Hu Yanan
Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Department of Orthopedic Surgery, Suzhou Yongding Hospital, Suzhou, Jiangsu Province, China.
Neural Regen Res. 2026 Apr 1;21(4):1304-1321. doi: 10.4103/NRR.NRR-D-24-01354. Epub 2025 Mar 25.
Spinal cord injuries have overwhelming physical and occupational implications for patients. Moreover, the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and resources, adding a substantial burden to the healthcare system and patients' families. In this context, chondroitinase ABC, a bacterial enzyme isolated from Proteus vulgaris that is modified to facilitate expression and secretion in mammals, has emerged as a promising therapeutic agent. It works by degrading chondroitin sulfate proteoglycans, cleaving the glycosaminoglycanchains of chondroitin sulfate proteoglycans into soluble disaccharides or tetrasaccharides. Chondroitin sulfate proteoglycans are potent axon growth inhibitors and principal constituents of the extracellular matrix surrounding glial and neuronal cells attached to glycosaminoglycan chains. Chondroitinase ABC has been shown to play an effective role in promoting recovery from acute and chronic spinal cord injury by improving axonal regeneration and sprouting, enhancing the plasticity of perineuronal nets, inhibiting neuronal apoptosis, and modulating immune responses in various animal models. In this review, we introduce the classification and pathological mechanisms of spinal cord injury and discuss the pathophysiological role of chondroitin sulfate proteoglycans in spinal cord injury. We also highlight research advancements in spinal cord injury treatment strategies, with a focus on chondroitinase ABC, and illustrate how improvements in chondroitinase ABC stability, enzymatic activity, and delivery methods have enhanced injured spinal cord repair. Furthermore, we emphasize that combination treatment with chondroitinase ABC further enhances therapeutic efficacy. This review aimed to provide a comprehensive understanding of the current trends and future directions of chondroitinase ABC -based spinal cord injury therapies, with an emphasis on how modern technologies are accelerating the optimization of chondroitinase ABC development.
脊髓损伤对患者有着极其严重的身体和职业影响。此外,脊髓损伤所需的广泛且长期的医疗护理显著增加了医疗成本和资源,给医疗系统和患者家庭带来了沉重负担。在这种背景下,软骨素酶ABC作为一种有前景的治疗药物应运而生。它是一种从普通变形杆菌中分离出来的细菌酶,经过改造以利于在哺乳动物中表达和分泌。其作用机制是降解硫酸软骨素蛋白聚糖,将硫酸软骨素蛋白聚糖的糖胺聚糖链切割成可溶性二糖或四糖。硫酸软骨素蛋白聚糖是强效的轴突生长抑制剂,也是围绕附着于糖胺聚糖链的神经胶质细胞和神经元细胞的细胞外基质的主要成分。在各种动物模型中,软骨素酶ABC已被证明通过促进轴突再生和发芽、增强神经元周围网的可塑性、抑制神经元凋亡以及调节免疫反应,在促进急性和慢性脊髓损伤的恢复中发挥有效作用。在这篇综述中,我们介绍了脊髓损伤的分类和病理机制,并讨论了硫酸软骨素蛋白聚糖在脊髓损伤中的病理生理作用。我们还重点介绍了脊髓损伤治疗策略的研究进展,特别是软骨素酶ABC,并阐述了软骨素酶ABC在稳定性、酶活性和递送方法方面的改进如何增强了受损脊髓的修复。此外,我们强调软骨素酶ABC的联合治疗进一步提高了治疗效果。这篇综述旨在全面了解基于软骨素酶ABC的脊髓损伤治疗的当前趋势和未来方向,重点关注现代技术如何加速软骨素酶ABC开发的优化。